Dorus et al. have provided evidence of genetic control of in vitro red blood cell (RBC) lithium (Li) distribution and in vivo RBC Li distribution (RBC Li/plasma Li ratio) using a monozygotic-dizygotic twin study method. Since in vitro and in vivo RBC Li/plasma Li ratios are significantly correlated, the in vitro assay provides a method for studying Li distribution in normal subjects. The first purpose of the proposed research is the study of in vitro RBC Li distribution in normal families. A preliminary analysis of data indicates that between-family variance is significantly greater than within-family variance, providing additional documentation of genetic control of Li distribution of RBC Li in manic depressive patients has received increasing attention. There is evidence that the RBC Li/plasma Li ratios of patients responding to lithium carbonate are higher than those of non-responders and that ratios of patients differ from those of normal controls. With regard to the etiology of manic depressive illness, an important question is whether the difference in cell membrane function is an inherent, and possibly genetically controlled, characteristic of manic depressive illness, or whether it is related to the pathological state. The second purpose of the proposed research is to assess in vitro RBC Li distribution in first degree relatives of bipolar probands and normal controls. If manic depressive illness is genetically transmitted, it is reasonable to assume that first degree relatives have a greater genetic predisposition to manic depressive illness the normal controls. Thus, if RBC Li distributions of first degree relatives differ significantly from those of normal controls, evidence will be provided that cell membrane function is central to the understanding of the genetic transmission of manic depressive illness.